EXPRESSION OF A TRANSACTIVATION-DEFICIENT FORM OF THYROID TRANSCRIPTION FACTOR-I DECREASES THE ACTIVITY OF CO-TRANSFECTED THYROGLOBULIN ANDTHYROPEROXIDASE PROMOTERS

Thyroid transcription factor I(TTF-1) plays a critical role in thyroid organogenesis and in the control of expression of several thyroid-spe cific genes, like those coding for thyroglobulin and thyroperoxidase. We have expressed the isolated DNA-binding homeodomain of TTF-I in cul tured thyroid cells by transient transfection. A specific reduction in the activity of cotransfected thyroglobulin and thyroperoxidase promo ters was observed in the presence of the isolated TTF-1 homeodomain, a s compared to their activity measured in the presence of a mutated hom eodomain unable to bind DNA. The activity of the SV40 early promoter, used as a control, was only marginally affected in these experiments. The transactivation-deficient form of TTF-1 described here may thus be used for investigating other cellular processes that are dependent on TTF-1 transcriptional activity.